October 30, 2012

A group of researchers in Israel, the United States and other nations have made important advances in the rapidly-expanding field of "regenerative medicine," outlining for the first time connections in genetic regulation that normally prevent birth defects in heart and facial muscles.

Some of these problems are surprisingly common – about 1 percent of all people have a congenital heart defect. This basic research will provide a road map to ultimately allow scientists to grow the cell types needed to repair such defects, from stem cells that can be generated from a person's own body.

"Advances in regenerative medicine and developmental biology can now happen because we no longer require human embryos to generate stem cells," said Chrissa Kioussi, a co-author on the study and associate professor in the College of Pharmacy at Oregon State University. "The Nobel Prize this year was awarded to people who discovered how to make stem cells from adult biopsies."

Patient-derived stem cells can in principle be turned into any needed cell type, Kioussi said. The key is understanding the exact regulatory process than tells cells what type they are supposed to turn into, she said, such as a cell on the outside of the left ventricle of the heart.

"Once we understand these genetic controls in sufficient detail, we can not only turn a skin cell into a stem cell, but also turn that stem cell into the type needed for the patient to recover," Kioussi said. "We may eventually be able to grow replacement organs from the patient's cells."

In this study, researchers identified four specific "transcription factor" genes that control processes related to heart and head muscle formation. When there are defects in this process, the result can be death or a range of debilitating problems, from cleft palate to facial malformations and defective heart valves.

"There are about 20,000 genes in the human genome, but only 2,000 of the genes describe transcription factors," Kioussi said. "These transcription factors control the output of genes, the genetic machinery. They collectively determine which of the 20,000 possible molecular machines is actually deployed in each particular cell type."

Scientists have found that these transcription factors don't work alone to define cell types in mammalian development – they function in small, self-stabilizing combinations of at least two or three.

The process moves rapidly after conception, and within one month most of the cells in the body "know" their cell type, based on the precise combination of transcription factors produced within them. When researchers understand how these stable transcription factor combinations get generated, they will know how to artificially generate these combinations in stem cells to convert them into the needed cell types.

Mammalian embryonic development is a process of self construction, a series of transitions of "temporary" cell types on the way to adult cell types. A fertilized egg is essentially a stem cell with the potential to become any other cell type. At each intermediate stage, the "temporary" cell types become more restricted in what they can become, until they ultimately achieve and maintain the adult type.

"In this work and in regenerative medicine, we care a great deal about all of these steps of cell differentiation," Kioussi said. "If you know all the steps it takes to get from here to there, you can identify what went wrong and find ways to fix it. This is being done already with some disease problems, and this work will move us closer to being able to repair heart and craniofacial defects."

The task is complex, Kioussi said, but very possible. Although there are 100 trillion cells in the human body, there are only about 100 adult cell types. Understanding and influencing the genetic specification of those cell types is possible and will probably revolutionize the treatment of many defects and diseases, Kioussi said.

This work was supported by the European Research Council, the Israel Science Foundation, the U.S. National Institutes of Health, and other agencies. The lead author was Eldad Tzahor at the Weizman Institute of Science in Israel, and other collaborators were from universities and agencies in the United Kingdom, India and Spain.

Researchers from the Haematopoietic Differentiation and Stem Cell Biology group at the Centre for Genomic Regulation (CRG), have described one of the mechanisms by which a cell (from the skin, for example) can be converted ...

Investigators at the Massachusetts General Hospital (MGH) Center for Regenerative Medicine and the Harvard Stem Cell Institute (HSCI) have found that Sox2  one of the transcription factors used in the conversion of ...

Researchers at the Gladstone Institute of Cardiovascular Disease (GICD) and the University of California, San Francisco have identified for the first time how tiny genetic factors called microRNAs may influence the differentiation ...

Recommended for you

(Phys.org)—That there are universal patterns in the naming of colors across languages has long been a topic of discussion in a range of disciplines, including anthropology, cognitive science and linguistics. However, previous ...

(Phys.org)—A team of researchers with members from several institutions in China has calculated what they believe is the minimum amount of land preservation needed to sustain wild giant panda populations. In their paper ...

The differences in how male and female fruit flies resist and adapt to oxidative stress may shed new light on how age-related diseases such as Alzheimer's and Parkinson's affect men and women differently.

Many infectious pathogens are difficult to treat because they develop into biofilms, layers of metabolically active but slowly growing bacteria embedded in a protective layer of slime, which are inherently more resistant ...

Researchers have discovered a way to program cells to inhibit CRISPR-Cas9 activity. "Anti-CRISPR" proteins had previously been isolated from viruses that infect bacteria, but now University of Toronto and University of Massachusetts ...

0 comments

Please sign in to add a comment.
Registration is free, and takes less than a minute.
Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.